The long-term objective of the research described in this application is to understand the role of ion transport in pancreatic endocrine secretion. In order to overcome previous methodological limits the recently developed in vitro perfusion preparation of the channel catfish Brockmann body will be used. This preparation has the following advantages considered crucial to the proposed project: 1) the organ is kept in a nearly physiological state, 2) the Brockmann body contains A-, B-, and D-cells at almost equal proportion, 3) the endocrine tissue makes up ca. 50% of the Brockmann body, and 4) the preparation has a long life-time. The investigation is aimed at a rigorous comparison of the characteristics of the cells responsible for the release of the pancreatic hormones. The yet uninvestigated release of the recently discovered somatostatin-22 will be included in this project because these measurements alone are of immense physiologic and pharmacologic interest. The following sub-objectives will be pursued: 1) Identify the stimuli for the release of somatostatin-22 and compare them with those of somatostatin-14. If appropriate, determine the dose-response curve for glucose-induced somatostatin-22 release. 2) Determine the effect of replacing extracellular sodium by an impermeable cation on the release of pancreatic hormones in response to various stimuli. Test the effects of activators and inhibitors of a voltage-sensitive sodium channel. 3) Characterize in detail the requirement of hormone release for extracellular calcium. 4) Monitor changes in membrane potential by the use of lipophilic cations. 5) Compare the requirements for the release of insulin, glucagon, somatostatin-14 and somatostatin-22 for extracellular cations. Integrate the data gathered under aims 1 through 4 to obtain a tentative sequence of ionic events governing secretion.